Association between circulating anti-HLA IgG antibodies and adverse events in heart transplant recipients

Objective: to study the relationship between circulating anti-HLA antibodies and the incidence of adverse events (death and retransplantation) and to evaluate the effectiveness of targeted therapies for graft dysfunction.

Materials and methods. A retrospective study was conducted among heart transplant recipients hospitalized with signs of circulatory failure (graft dysfunction). All patients underwent coronary angiography, endomyocardial biopsy, and serological testing for anti-HLA IgG antibodies at baseline and, when applicable, after treatment. All heart transplant recipients underwent endomyocardial biopsy with examination of six tissue samples using histological and immunohistochemical techniques, and coronary angiography. Anti-HLA IgG levels in serum were measured using a Luminex device. Follow-up anti-HLA IgG testing was performed only in patients with initially detectable antibodies and after administration of specific therapies for presumed graft rejection.

Results. The study included 362 heart transplant recipients observed at Shumakov National Medical Research Center of Transplantology and Artificial Organs between January 2018 and November 2024. Participants were aged 18–72 years (mean 48.1 ± 1.3 years) with a mean post-transplant follow-up of 1343.6 ± 125.1 days (95% CI 1218.5–1408.6), comprising 69 females and 293 males. Anti-HLA IgG antibodies were detected in 111 recipients (30.7%). Univariate analysis identified significant associations between adverse events and: repeat heart transplantation (p = 0.005), perioperative use of mechanical circulatory support (p < 0.003), age under 46 years at hospitalization (p = 0.023), and anti-HLA II maxMFI above 5000 (p = 0.042). Regression analysis adjusted for anti-HLA II levels showed that only initially elevated anti-HLA II maxMFI levels (>5000) and the persistence of any anti-HLA II levels after etiotropic treatment were associated with the risk of adverse events.

Conclusion. In heart recipients hospitalized with signs of circulatory failure due to graft dysfunction, the presence of anti-HLA II maxMFI titers above 5000 at baseline, as well as residual anti-HLA II titers after etiotropic treatment for antibody-mediated rejection, are independent predictors of adverse events, including retransplantation and death.

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